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    Animal Model Having a Chimeric Human Liver and Susceptible to Human Hepatitis C Virus Infection
    3.
    发明申请
    Animal Model Having a Chimeric Human Liver and Susceptible to Human Hepatitis C Virus Infection 有权
    具有嵌合人肝脏并易于感染人类丙型肝炎病毒感染的动物模型

    公开(公告)号：US20090151012A1

    公开(公告)日：2009-06-11

    申请号：US12333002

    申请日：2008-12-11

    申请人： NORMAN M. KNETEMAN ,  D. Lorne Tyrrell ,  David Frederick Mercer

    发明人： NORMAN M. KNETEMAN ,  D. Lorne Tyrrell ,  David Frederick Mercer

    IPC分类号： G01N33/564 ,  A01K67/027

    CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0337 ,  C07K14/765 ,  C12N9/6424 ,  C12N15/63

    摘要： The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

    摘要翻译： 本发明的特征在于非人动物模型，其易受人类肝营养性病原体特别是人丙型肝炎病毒（HCV）的感染。 该模型基于具有人 - 小鼠嵌合肝的非人免疫受损转基因动物，其中转基因提供在肝脏中表达尿激酶型纤溶酶原激活物。 本发明还涉及用于鉴定候选治疗剂的方法，例如具有抗HCV感染的抗病毒活性的试剂。 本发明的动物也可用于评估各种药物的毒性，以及药物在降低血脂中的活性。

    Chimeric antigens for eliciting an immune response
    4.
    发明授权
    Chimeric antigens for eliciting an immune response 有权
    用于引发免疫应答的嵌合抗原

    公开(公告)号：US08029803B2

    公开(公告)日：2011-10-04

    申请号：US10365620

    申请日：2003-02-13

    申请人： Rajan George ,  Lorne Tyrrell ,  Antoine Noujaim

    发明人： Rajan George ,  Lorne Tyrrell ,  Antoine Noujaim

    IPC分类号： A61K399/29 ,  C12P21/00

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/385 ,  A61K2039/57 ,  A61K2039/6056 ,  C07K2319/00 ,  C07K2319/01 ,  C07K2319/21 ,  C07K2319/30 ,  C12N2710/14143 ,  C12N2730/10122 ,  C12N2770/24222

    摘要： Disclosed herein are the nucleotide sequences, deduced amino acid sequences as well as methods and compositions necessary to elicit immune responses against chronic Hepatitis B infections in animals and humans. Immune response is enhanced by fusing relevant viral antigens with xenotypic immunoglobulin heavy chain region through a peptide linker and producing the fusion proteins in Baculovirus expression system to incorporate high mannose glycosylation. By virtue of the antibody component, the fusion proteins bind to Fc receptors on the surface of antigen presenting cells, are taken up, processed and derived peptides are presented on MHC Class I, which elicit a CTL (Th1) response. In a similar fashion, due to cross priming and presentation on MHC Class II, will elicit a humoral (Th2) response. In addition, disclosed are the methods of cloning, expression and production of the fusion proteins.

    摘要翻译： 本文公开了核苷酸序列，推定的氨基酸序列以及在动物和人中引发针对慢性乙型肝炎感染的免疫应答所必需的方法和组合物。 通过肽接头将相关病毒抗原与异型免疫球蛋白重链区融合并在杆状病毒表达系统中产生融合蛋白以掺入高甘露糖糖基化来增强免疫应答。 由于抗体组分，融合蛋白与抗原呈递细胞表面上的Fc受体结合，被吸收，加工，并且衍生的肽呈现在引起CTL（Th1）应答的MHC I类上。 以类似的方式，由于交叉引物和介绍MHC II类，将引发体液（Th2）反应。 此外，公开了融合蛋白的克隆，表达和产生的方法。

    Animal model having a chimeric human liver
    7.
    发明授权
    Animal model having a chimeric human liver 有权
    具有嵌合人肝脏的动物模型

    公开(公告)号：US07498479B2

    公开(公告)日：2009-03-03

    申请号：US11517941

    申请日：2006-09-07

    申请人： Norman M. Kneteman ,  D. Lorne Tyrrell ,  David F. Mercer

    发明人： Norman M. Kneteman ,  D. Lorne Tyrrell ,  David F. Mercer

    IPC分类号： A01K67/00 ,  A01K67/033 ,  A01K67/027 ,  C12N15/00

    CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0337 ,  C07K14/765 ,  C12N9/6424 ,  C12N15/63

    摘要： The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

    摘要翻译： 本发明的特征在于非人动物模型，其易受人类肝营养性病原体特别是人丙型肝炎病毒（HCV）的感染。 该模型基于具有人 - 小鼠嵌合肝的非人免疫受损转基因动物，其中转基因提供在肝脏中表达尿激酶型纤溶酶原激活物。 本发明还涉及用于鉴定候选治疗剂的方法，例如具有抗HCV感染的抗病毒活性的试剂。 本发明的动物也可用于评估各种药物的毒性，以及药物在降低血脂中的活性。

    Animal Model Having a Chimeric Human Liver and Suceptible to Human Hepatitis C Virus Infection
    9.
    发明申请
    Animal Model Having a Chimeric Human Liver and Suceptible to Human Hepatitis C Virus Infection 有权
    具有嵌合人肝脏和易感人类丙型肝炎病毒感染的动物模型

    公开(公告)号：US20110167507A1

    公开(公告)日：2011-07-07

    申请号：US12840188

    申请日：2010-07-20

    申请人： Norman M. Kneteman ,  D. Lorne Tyrrell ,  David Frederick Mercer

    发明人： Norman M. Kneteman ,  D. Lorne Tyrrell ,  David Frederick Mercer

    IPC分类号： A01K67/027

    CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0337 ,  C07K14/765 ,  C12N9/6424 ,  C12N15/63

    摘要： The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

    摘要翻译： 本发明的特征在于非人动物模型，其易受人类肝营养性病原体特别是人丙型肝炎病毒（HCV）的感染。 该模型基于具有人 - 小鼠嵌合肝的非人免疫受损转基因动物，其中转基因提供在肝脏中表达尿激酶型纤溶酶原激活物。 本发明还涉及用于鉴定候选治疗剂的方法，例如具有抗HCV感染的抗病毒活性的试剂。 本发明的动物也可用于评估各种药物的毒性，以及药物在降低血脂中的活性。